The goal of this research proposal is to examine the modulation, by steroid and peptide hormones, of gene expression during mouse mammary tumorigenesis. These studies will focus on mouse mammary tumor virus (MMTV) expression in preneoplastic (alveolar nodule outgrowth lines) and neoplastic (derived from nodule lines) mammary tissues in syngeneic high (BALB/cfC3H), moderate (BALB/cVo) and low (BALB/c) mammary tumor incidence strains. Attention will also be directed toward analysis of casein mRNA expression which will be utilized as a biochemical marker of differentiated mammary tissue function. Selective hybridization probes for MMTV RNA and casein mRNA will be used to quantitate RNA and DNA levels in nodules and tumors. Experiments will be carried out primarily in vitro, using an organ culture system which permits precise manipulation of the hormone evironment and provides a culture system in which to measure the hormonal effects on MMTV synthesis and turnover. Cytological studies, including in situ hybridization and immunochemical staining, will be carried out in order to identify the cellular population(s) in preneoplastic and neoplastic mammary lesions that synthesize MMTV and casein and are hormone-responsive. The proposed studies should contribute to our understanding of the interaction of hormonal and viral factors in mammary tumorigenesis.